H2A.Z.1 Monoubiquitylation Antagonizes BRD2 to Maintain Poised Chromatin in ESCs
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Surface-2016-H2A.Z.1 Monoubiquity.pdf
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Author(s)
Surface, Lauren E.
Fields, Paul A.
Subramanian, Vidya
Behmer, Russell
Udeshi, Namrata
Peach, Sally E.
Carr, Steven A.
Jaffe, Jacob D.
Fields, Paul A.
Boyer, Laurie Ann
Date Issued
January 2016
Journal
Cell Reports
Publisher
Elsevier
Citation
Surface, Lauren E., Paul A. Fields, Vidya Subramanian, Russell Behmer, Namrata Udeshi, Sally E. Peach, Steven A. Carr, Jacob D. Jaffe, and Laurie A. Boyer. “H2A.Z.1 Monoubiquitylation Antagonizes BRD2 to Maintain Poised Chromatin in ESCs.” Cell Reports 14, no. 5 (February 2016): 1142–1155.
Version
Final published version
Abstract
Histone variant H2A.Z occupies the promoters of active and poised, bivalent genes in embryonic stem cells (ESCs) to regulate developmental programs, yet how it contributes to these contrasting states is poorly understood. Here, we investigate the function of H2A.Z.1 monoubiquitylation (H2A.Z.1ub) by mutation of the PRC1 target residues (H2A.Z.1[superscript K3R3]). We show that H2A.Z.1[superscript K3R3] is properly incorporated at target promoters in murine ESCs (mESCs), but loss of monoubiquitylation leads to de-repression of bivalent genes, loss of Polycomb binding, and faulty lineage commitment. Using quantitative proteomics, we find that tandem bromodomain proteins, including the BET family member BRD2, are enriched in H2A.Z.1 chromatin. We further show that BRD2 is gained at de-repressed promoters in H2A.Z.1[superscript K3R3] mESCs, whereas BRD2 inhibition restores gene silencing at these sites. Together, our study reveals an antagonistic relationship between H2A.Z.1ub and BRD2 to regulate the transcriptional balance at bivalent genes to enable proper execution of developmental programs.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
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DOI of Published Version
https://doi.org/10.1016/j.celrep.2015.12.100
